1. Field of the Invention
The present invention generally relates to methods of diagnosing and treating inflammation, particularly inflamed atherosclerotic plaque at risk of rupture or thrombosis. More particularly, the methods of the invention pertain to the simultaneous detection of two or more chemical parameters associated with inflammation and/or active cellular metabolism in plaque. The invention also relates to multi-parameter catheter assemblies for irradiating sites along a blood vessel wall with near-infrared and visible wavelength radiation and for receiving and analyzing the reflected radiation to qualitatively or quantitatively determine the status of each such parameter.
2. Description of the Related Art
Atherosclerotic coronary artery disease is the leading cause of death in industrialized countries. Typically, patients who have died of coronary disease may exhibit as many as several dozen atherosclerotic plaques in the arterial tree. Plaque, a thickening in the arterial vessel wall, results from the accumulation of cholesterol, proliferation of smooth muscle cells, secretion of a collagenous extracellular matrix by the cells, and accumulation of inflammatory cells and, eventually, hemorrhage, thrombosis and calcification.
Narrowing of the arteries feeding an organ, such as the heart, decreases the flow of blood supplying oxygen and necessary energy substrates to the active cells of the organ. This defect is more pronounced once the organ increases its metabolic activity: this demands an even greater supply which cannot be satisfied due to the inappropriate perfusion resulting from the narrowing. Myocardial ischemia (insufficiency of blood perfusion) is the clinical sign of atherosclerosis characterized by chest discomfort (angina). Over the past decades, several clinical and laboratory tools (such as exercise tests, angiography, and perfusion scans) and therapeutic methods (such as angioplasty, coronary bypass surgery, and atherectomy) have been developed in order to diagnose and treat atherosclerotic disease. These methods are based on the concepts of detecting and treating lumen stenosis (significant narrowing).
Various fiber optic therapeutic catheters have been developed some of which, including the “smart laser” types, attempt to distinguish healthy tissue from atheromatous plaque. For example, U.S. Pat. No. 5,106,387, issued to Kittrell et al., describes such a device. However, the “smart laser” catheter was disappointing in clinical trials (M. B. Leon, M. D., personal communication), and never became an accepted therapy.
Helfer et al. discloses in U.S. Pat. No. 5,197,470 another method of discriminating healthy tissue from diseased tissue in a blood vessel based on characteristic near-infrared reflectance wavelengths attributable to “diseased” or “healthy” conditions. For the purpose of evaluating blood vessel tissue, “diseased” (i.e., plaque) or “healthy” status was determined in those studies by a skilled pathologist who examined each specimen for the presence of cholesterol esters and calcification as the primary distinguishing features. These investigators noted the difficulty of defining and quantifying what is a “diseased state” of the tissue for obtaining meaningful comparative numbers. As with most known methods and devices directed at identifying plaque in a living vessel, this method relies only on anatomo-pathological (histo-pathological) aspects of the plaque. Such features as calcification and cholesterol content are now considered to be poor indicators of the truly dangerous plaques, as discussed very recently in an American Heart Association Monograph entitled “The Vulnerable Atherosclerotic Plaque,” Valentine Fuster, M.D., Ph.D., ed., Futura Publishing Co., Armonk, N.Y. (1998).